Traumatic brain injury (TBI) is a major cause of death and chronic disability in the US. The combinations of direct medical expense (~60 BILLION USD annually!), lost income and long-term support are staggering. Early diagnosis and evidence-based treatments are critical to improve outcome after TBI reducing direct and indirect costs and importantly human suffering. This proposal addresses the issue of improving early diagnosis through proteomics analysis of brain microdialysates, CSF and blood samples in relation to clinical data and long-term outcome. Cerebral microdialysis (cMD) is a minimally invasive technique that samples the brain extracellular fluid (bECF) and provides vital information about ongoing metabolic changes in TBI in neurointensive units. Changes in the serum and/or CSF levels of protein biomarkers can be easily determined and can indicate specific pathological changes triggered by the injury. The exact relationship between changes in protein biomarkers in the different biological compartments are currently unknown. As part of an ongoing collaborative effort with the Karolinska University Hospital, Stockholm, Sweden we have collected bECF, CSF and blood samples at every 6 to 12 hrs from 17 TBI patients up to 7 days post- injury. The objective of this proposal is to identify and compare the pattern of changes of neuron and glia specific biomarkers through proteomics analysis among the three bio fluids. Our rationale is that if we establish the relationship between the injury-induced changes in protein biomarkers in the bECF, CSF and serum, we can improve the diagnostic value of changes measured in CSF and serum.